homoharringtonine | 850694-15-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 三尖杉生物碱
• 英文名称: homoharringtonine
• 英文别名: (R)-2-hydroxy-2-(4-hydroxy-4-methyl-pentyl)-succinic acid 1-((3aR)-2-methoxy-(3arC⁴,14bc)-1,5,6,8,9,14b-hexahydro-4H-cyclopenta[b][1,3]dioxolo[4',5':4,5]benzo[1,2-d]pyrrolo[1,2-a]azepin-1t-yl) ester 4-methyl ester；cephalotaxine, 4-methyl-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanediocate ester；Homodeoxyharringtonin；Homoharringtonin；1-O-[(2S,3S,6R)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.02,6.06,10.015,19]icosa-1(20),4,13,15(19)-tetraen-3-yl] 4-O-methyl 2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate
• CAS: 850694-15-4
• 化学式: C₂₉H₃₉NO₉
• 分子量: 545.63
• InChiKey: HYFHYPWGAURHIV-BRXDYEKISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  L-苹果酸 、 homoharringtonine 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  [EN] WATER SOLUBLE CRYSTALLIN SALTS OF CERTAIN HARRINGTONINES UNAMBIGUOUSLY PROTONATED ON THEIR ALKALOID NITROGEN AND THEIR USE AS CHEMOTHERAPEUTIC DRUGS
  [FR] SELS CRISTALLINS SOLUBLES DANS L'EAU DE CERTAINES HARRINGTONINES PROTONÉES SANS AMBIGÜITÉ SUR LEUR AZOTE ALCALOÏDE ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS CHIMIOTHÉRAPEUTIQUES

  摘要：

  本发明涉及在固态分析中观察到质子化氮的哈林顿碱盐，具有公式（1），包括溶剂化物，由公式（2）的头状税碱酯反应制成，其中R1是但不限于烷基，芳基，环烷基，杂基烷基，杂芳基或杂环烷基，R2是独立的但不限于H，烷基，芳基，环烷基，杂基烷基，杂芳基或杂环烷基，与一种具有一般式AH的酸在结晶溶剂中，所述盐的水或醇溶性范围约为5 mg / mL至约100 mg / Ml。本发明还涉及制备这些盐的过程及其作为化疗药物的用途。

  公开号：

  WO2015101628A1
• 作为产物：
  描述：

  2-甲基环戊-1-烯-1-甲醛 在 草酰氯 、 臭氧 、 zinc(II) chloride 、 silver(l) oxide 作用下， 以 四氢呋喃 为溶剂， 生成 homoharringtonine
  参考文献：
  名称：

  Synthesis of homoharringtonine and its derivative .

  摘要：

  DOI：

  10.1016/s0040-4039(00)87634-0

文献信息

• HARRINGTONINES SALTS, IN PARTICULAR RETINOATES, THEIR PROCESS OF PREPARATION AND THEIR USES IN THE TREATMENT OF LEUKEMIAS, CANCERS, AUTOIMMUNE, SKIN, ALZHEIMER'S AND INFLAMMATORY BOWEL DISEASES AND VIRAL INFECTIONS, COMBINED WITH MYELOPOIESIS STIMULATING AGENTS
  申请人：Robin, Jean-Pierre

  公开号：EP3763715A1

  公开（公告）日：2021-01-13

  The present invention relates to salt of the following formula (I): Another object of the invention is a method for preventing or treating diseases selected among cancer, leukemias, lymphomas, myelodysplastic syndrome, autoimmune diseases, skin diseases, neurological diseases such as Alzheimer's disease, inflammatory bowel disease, such as Crohn's disease, and viral infections including papillomavirus comprising administering to a patient in need thereof an effective dose of the salt of formula (I) or a pharmaceutical composition comprising thereof. The present invention also relates to a method of preparation of the salt of formula (I).

  本发明涉及以下式(I)的盐： 另一个本发明的目的是提供一种用于预防或治疗所选疾病的方法，所选疾病包括癌症、白血病、淋巴瘤、骨髓增生异常综合症、自身免疫性疾病、皮肤病、神经系统疾病如阿尔茨海默病、炎症性肠病如克罗恩病，以及包括乳头状瘤病毒在内的病毒感染，其包括向需要该盐的患者施用公式(I)的盐或包含其的药物组合物的有效剂量。 本发明还涉及制备公式(I)的盐的方法。
• Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo
  申请人：Brown Dennis M.

  公开号：US10383847B2

  公开（公告）日：2019-08-20

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutically active agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo. In particular, the therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo, are effective Nek9 inhibitors. The active agent, such as meisoindigo, can act as a Nek9 inhibitor. The active agent can be used together with Nek9 inhibitors or agents that inhibit the expression of Nek9.

  本发明描述了通过提高单一疗法的疗效或减少副作用来提高以前受次优治疗性能限制的治疗活性制剂的疗效的方法和组合物。这种方法和组合物特别适用于选自以下组别的治疗活性剂：(i) 靛红素；(ii) 靛红素的类似物；(iii) 靛红素或靛红素类似物的衍生物；(iv) 包含靛红素、靛红素类似物或靛红素或靛红素类似物衍生物的药物组合物，特别是甲异靛。特别是，选自以下组别的治疗活性剂是有效的 Nek9 抑制剂：(i) 靛红素；(ii) 靛红素的类似物；(iii) 靛红素的衍生物或靛红素的类似物；以及 (iv) 由靛红素、靛红素的类似物或靛红素的衍生物或靛红素的类似物，特别是 meisoindigo 组成的药物组合物。活性剂，如 meisoindigo，可作为 Nek9 抑制剂。活性剂可与 Nek9 抑制剂或抑制 Nek9 表达的制剂一起使用。
• Compositions to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
  申请人：Race Oncology Ltd.

  公开号：US10548876B2

  公开（公告）日：2020-02-04

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.

  本发明描述了通过提高单一疗法的疗效或减少副作用来改善以前因治疗效果不理想而受到限制的治疗剂的疗效的方法和组合物。这些方法和组合物尤其适用于双蒽或其衍生物、类似物或原药。
• Methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof
  申请人：ALBANY MOLECULAR RESEARCH, INC.

  公开号：US10597401B2

  公开（公告）日：2020-03-24

  The present invention relates to methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof. The resulting products are useful in the treatment of proliferative diseases and infectious diseases.

  本发明涉及奥美他辛及其头孢他辛衍生物的制备方法和中间体。所得产品可用于增殖性疾病和传染性疾病的治疗。
• Combinatorial methods to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
  申请人：Race Oncology Ltd.

  公开号：US11147800B2

  公开（公告）日：2021-10-19

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.

  本发明描述了通过提高单一疗法的疗效或减少副作用来改善以前因治疗效果不理想而受到限制的治疗剂的疗效的方法和组合物。这些方法和组合物尤其适用于双蒽或其衍生物、类似物或原药。